Dr. Tik is a postdoctoral scholar from Vienna, Austria. He has a background in Biological Psychology and Medical Physics and experience in highly interdisciplinary experimental research. During his academic career he used brain imaging and stimulation methods to gain insights into pathways related to insightful problem solving as well as emotion processing. Through collaboration between the Medical University of Vienna and international partners, he could further identify connectivity changes linked to affective disorders and treatment.
Specifically, Dr. Tik has developed new techniques to better combine Transcranial Magnetic Stimulation with functional Magnetic Resonance Imaging to measure induced activation changes as they happen.
Dr. Tik recently joined the Stanford Brain Stimulation Laboratory team to translate these research tools into clinical applications aiming to optimise important stimulation parameters for tailoring transcranial magnetic stimulation to individual patient's needs.

Honors & Awards

  • Merit Abstract Award, Organization for Human Brain Mapping (OHBM) (2021)
  • Travel Award, Bio-X (2021)
  • Visiting scholarships AI, Bavaria California Technology Center (2021)
  • Janssen Special Award, / Janssen (Johnson&Johnson) (2018)
  • Merit Abstract Award, OHBM (2017)
  • Best Abstract Award, Interdisciplinary College (2015)
  • Merit Abstract Award, OHBM (2015)

Boards, Advisory Committees, Professional Organizations

  • Organising commitee, International Workshop on Concurrent TMS/fMRI (2022 - Present)
  • Management committee, COST Action 18138 - RISE Network in Peripartum Depression Disorder (2019 - Present)
  • Program committee, Brain Stimulation and Imaging Meeting, BrainSTIM (2019 - 2019)

Stanford Advisors

Lab Affiliations

All Publications

  • Concurrent TMS-fMRI: Technical Challenges, Developments, and Overview of Previous Studies. Frontiers in psychiatry Mizutani-Tiebel, Y., Tik, M., Chang, K., Padberg, F., Soldini, A., Wilkinson, Z., Voon, C. C., Bulubas, L., Windischberger, C., Keeser, D. 2022; 13: 825205


    Transcranial magnetic stimulation (TMS) is a promising treatment modality for psychiatric and neurological disorders. Repetitive TMS (rTMS) is widely used for the treatment of psychiatric and neurological diseases, such as depression, motor stroke, and neuropathic pain. However, the underlying mechanisms of rTMS-mediated neuronal modulation are not fully understood. In this respect, concurrent or simultaneous TMS-fMRI, in which TMS is applied during functional magnetic resonance imaging (fMRI), is a viable tool to gain insights, as it enables an investigation of the immediate effects of TMS. Concurrent application of TMS during neuroimaging usually causes severe artifacts due to magnetic field inhomogeneities induced by TMS. However, by carefully interleaving the TMS pulses with MR signal acquisition in the way that these are far enough apart, we can avoid any image distortions. While the very first feasibility studies date back to the 1990s, recent developments in coil hardware and acquisition techniques have boosted the number of TMS-fMRI applications. As such, a concurrent application requires expertise in both TMS and MRI mechanisms and sequencing, and the hurdle of initial technical set up and maintenance remains high. This review gives a comprehensive overview of concurrent TMS-fMRI techniques by collecting (1) basic information, (2) technical challenges and developments, (3) an overview of findings reported so far using concurrent TMS-fMRI, and (4) current limitations and our suggestions for improvement. By sharing this review, we hope to attract the interest of researchers from various backgrounds and create an educational knowledge base.

    View details for DOI 10.3389/fpsyt.2022.825205

    View details for PubMedID 35530029

  • EMOTION PROCESSING TASK AS A NEW STRATEGY FOR LOCATING INDIVIDUALIZED TMS TARGETS Vasileiadi, M., Tik, M., Kranz, G., Ruetgen, M., Princic, M., Vanicek, T., Pfabigan, D. M., Hahn, A., Sladky, R., Lanzenberger, R., Lamm, C., Windischberger, C. MEDICINSKA NAKLADA. 2022: 27
  • POTENTIAL OF ELECTRIC FIELD SIMULATIONS IN CLINICAL PRACTICE Baeken, C., Tik, M., Puonti, O., Klooster, D., Opitz, A., Vasileiadi, M. MEDICINSKA NAKLADA. 2022: 22-23
  • Give me a pain that I am used to: distinct habituation patterns to painful and non-painful stimulation. Scientific reports Paul, K., Tik, M., Hahn, A., Sladky, R., Geissberger, N., Wirth, E., Kranz, G. S., Pfabigan, D. M., Kraus, C., Lanzenberger, R., Lamm, C., Windischberger, C. 2021; 11 (1): 22929


    Pain habituation is associated with a decrease of activation in brain areas related to pain perception. However, little is known about the specificity of these decreases to pain, as habituation has also been described for other responses like spinal reflexes and other sensory responses. Thus, it might be hypothesized that previously reported reductions in activation are not specifically related to pain habituation. For this reason, we performed a 3T fMRI study using either painful or non-painful electrical stimulation via an electrode attached to the back of the left hand. Contrasting painful vs. non-painful stimulation revealed significant activation clusters in regions well-known to be related to pain processing, such as bilateral anterior and posterior insula, primary/secondary sensory cortices (S1/S2) and anterior midcingulate cortex (aMCC). Importantly, our results show distinct habituation patterns for painful (in aMCC) and non-painful (contralateral claustrum) stimulation, while similar habituation for both types of stimulation was identified in bilateral inferior frontal gyrus (IFG) and contralateral S2. Our findings thus distinguish a general habituation in somatosensory processing (S2) and reduced attention (IFG) from specific pain and non-pain related habituation effects where pain-specific habituation effects within the aMCC highlight a change in affective pain perception.

    View details for DOI 10.1038/s41598-021-01881-4

    View details for PubMedID 34824311

  • Combining stimulus types for improved coverage in population receptive field mapping. NeuroImage Linhardt, D., Pawloff, M., Hummer, A., Woletz, M., Tik, M., Ritter, M., Schmidt-Erfurth, U., Windischberger, C. 2021; 238: 118240


    Retinotopy experiments using population receptive field (pRF) mapping are ideal for assigning regions in the visual field to cortical brain areas. While various designs for visual stimulation were suggested in the literature, all have specific shortcomings regarding visual field coverage. Here we acquired high-resolution 7 Tesla fMRI data to compare pRF-based coverage maps obtained with the two most commonly used stimulus variants: moving bars; rotating wedges and expanding rings. We find that stimulus selection biases the spatial distribution of pRF centres. In addition, eccentricity values and pRF sizes obtained from wedge/ring or bar stimulation runs show systematic differences. Wedge/ring stimulation results show lower eccentricity values and strongly reduced pRF sizes compared to bar stimulation runs. Statistical comparison shows significantly higher pRF centre numbers in the foveal 2° region of the visual field for wedge/ring compared to bar stimuli. We suggest and evaluate approaches for combining pRF data from different visual stimulus patterns to obtain improved mapping results.

    View details for DOI 10.1016/j.neuroimage.2021.118240

    View details for PubMedID 34116157

  • Dynamic causal modeling of the prefrontal-amygdala network during processing of emotional faces. Brain connectivity Sladky, R., Hahn, A., Karl, I. L., Geissberger, N., Kranz, G., Tik, M., Kraus, C., Pfabigan, D., Gartus, A., Lanzenberger, R., Lamm, C., Windischberger, C. 2021


    The importance of the amygdala - medial orbitofrontal cortex (OFC) network during processing of emotional stimuli, emotional faces in particular, is well established. This premise is supported by converging evidence from animal models, human neuroanatomical results, and neuroimaging studies. However, there is missing evidence from human brain connectivity studies that the OFC and no other prefrontal brain areas such as the DLPFC or VLPFC are responsible for amygdala regulation in the functional context of emotional face stimuli.Dynamic causal modeling of ultra-high field functional MRI data acquired at 7 Tesla in 38 healthy subjects and a well-established paradigm for emotional face processing were used to assess the central role of the OFC in order to provide empirical validation for the assumed network architecture.Using Bayesian model selection, it is demonstrated that indeed the OFC, and not the VLPFC and the DLPFC, down regulates amygdala activation during the emotion discrimination task. Additionally, Bayesian model averaging group results were rigorously tested using bootstrapping, further corroborating these findings and providing an estimator for robustness and optimal sample sizes.While it is true that VLPFC and DLPFC are relevant for the processing of emotional faces and are connected to the OFC, the OFC appears to be a central hub for prefrontal-amygdala interaction.

    View details for DOI 10.1089/brain.2021.0073

    View details for PubMedID 34605671

  • Detached empathic experience of others' pain in remitted states of depression - An fMRI study. NeuroImage. Clinical Rütgen, M., Pfabigan, D. M., Tik, M., Kraus, C., Pletti, C., Sladky, R., Klöbl, M., Woletz, M., Vanicek, T., Windischberger, C., Lanzenberger, R., Lamm, C. 2021; 31: 102699


    Major depressive disorder is strongly associated with impairments and difficulties in social interactions. Deficits in empathy, a vital skill for social interactions, have been identified as a risk factor for relapse. However, research on empathy in remitted states of depression is scarce. We chose a social neuroscience approach to investigate potentially altered neural processes involved in sub-components of empathy in remitted states of depression. We expected aberrations in cognitive components of empathy, based on previous reports regarding their role as risk factors for relapse.Employing functional magnetic resonance imaging and a pain empathy task (video clips of painful medical treatments), we compared behavioral and neural empathic responses of unmedicated remitted depressive patients (N = 32) to those of untreated acutely depressed patients (N = 29) and healthy controls (N = 35). Self-report ratings of pain evaluation and affect-sharing were obtained.Compared to controls and acutely depressed patients, remitted depressive patients reported higher pain evaluation and showed increased activity in the right temporo-parietal junction. This region, which is central to self-other distinction and which has been linked to adopting a detached perspective, also exhibited reduced connectivity to the anterior insula. Furthermore, we observed reduced activity in regions involved in emotion processing (amygdala) and perception of affective facial expressions (fusiform face area, posterior superior temporal sulcus).Remitted states of depression are associated with a detached empathic style in response to others' pain, characterized by increased self-other distinction, lowered affective processing, and reduced connectivity between empathy-related brain regions. Although this may prevent emotional harm in specific situations, it may reduce opportunities for positive experiences in social interactions in the long run.

    View details for DOI 10.1016/j.nicl.2021.102699

    View details for PubMedID 34049164

    View details for PubMedCentralID PMC8167276

  • Technical Note: Human tissue-equivalent MRI phantom preparation for 3 and 7 Tesla. Medical physics Woletz, M., Roat, S., Hummer, A., Tik, M., Windischberger, C. 2021


    While test objects (phantoms) in magnetic resonance imaging (MRI) are crucial for sequence development, protocol validation, and quality control, studies on the preparation of phantoms have been scarce, particularly at fields exceeding 3 Tesla. Here, we present a framework for the preparation of phantoms with well-defined T1 and T2 times at 3 and 7 Tesla.Phantoms with varying concentrations of agarose and Gd-DTPA were prepared and measured at 3 and 7 Tesla using T1 and T2 mapping techniques. An empirical, polynomial model was constructed that best represents the data at both field strengths, enabling the preparation of new phantoms with specified combinations of both T1 and T2 . Instructions for three different tissue types (brain gray matter, brain white matter, and renal cortex) are presented and validated.T1 times in the samples ranged from 698 to 2820 ms and from 695 to 2906 ms, whereas T2 times ranged from 39 to 227 ms and from 34 to 235 ms for 3 and 7 Tesla scans, respectively. Models for both relaxation times used six parameters to represent the data with an adjusted R² of 0.998 and 0.997 for T1 and T2 , respectively.Based on the equations derived from the current study, it is now possible to obtain accurate weight specifications for a test object with desired T1 and T2 relaxation times. This will spare researchers the laborious task of trail-and-error approaches in test object preparation attempts.

    View details for DOI 10.1002/mp.14986

    View details for PubMedID 34018625

  • Reproducibility of amygdala activation in facial emotion processing at 7T. NeuroImage Geissberger, N., Tik, M., Sladky, R., Woletz, M., Schuler, A. L., Willinger, D., Windischberger, C. 2020; 211: 116585


    Despite its importance as the prime method for non-invasive assessment of human brain function, functional MRI (fMRI) was repeatedly challenged with regards to the validity of the fMRI-derived brain activation maps. Amygdala fMRI was particularly targeted, as the amygdala's anatomical position in the ventral brain combined with strong magnetic field inhomogeneities and proximity to large vessels pose considerable obstacles for robust activation mapping. In this high-resolution study performed at ultra-high field (7T) fMRI, we aimed at (1) investigating systematic replicability of amygdala group-level activation in response to an established emotion processing task by varying task instruction and acquisition parameters and (2) testing for intra- and intersession reliability. At group-level, our results show statistically significant activation in bilateral amygdala and fusiform gyrus for each of the runs acquired. In addition, while fusiform gyrus activations are consistent across runs and sessions, amygdala activation levels show habituation effects across runs. This amygdala habituation effect is replicated in a session repeated two weeks later. Varying task instruction between matching emotions and matching persons does not change amygdala activation strength. Also, comparing two acquisition protocols with repetition times of either 700 ​ms or 1400 ​ms did not result in statistically significant differences of activation levels. Regarding within-subject reliability of amygdala activation, despite considerable variance in individual habituation patterns, we report fair to good inter-session reliability for the first run and excellent reliability for averages over runs. We conclude that high-resolution fMRI at 7T allows for robust mapping of amygdala activation in a broad range of variations. Our results of amygdala 7T fMRI are suitable to inform methodology and may encourage future studies to continue using emotion discrimination paradigms in clinical and non-clinical applications.

    View details for DOI 10.1016/j.neuroimage.2020.116585

    View details for PubMedID 31996330

  • Hippocampal Subfields in Acute and Remitted Depression-an Ultra-High Field Magnetic Resonance Imaging Study. The international journal of neuropsychopharmacology Kraus, C., Seiger, R., Pfabigan, D. M., Sladky, R., Tik, M., Paul, K., Woletz, M., Gryglewski, G., Vanicek, T., Komorowski, A., Kasper, S., Lamm, C., Windischberger, C., Lanzenberger, R. 2019; 22 (8): 513-522


    Studies investigating hippocampal volume changes after treatment with serotonergic antidepressants in patients with major depressive disorder yielded inconsistent results, and effects on hippocampal subfields are unclear.To detail treatment effects on total hippocampal and subfield volumes, we conducted an open-label study with escitalopram followed by venlafaxine upon nonresponse in 20 unmedicated patients with major depressive disorder. Before and after 12 weeks treatment, we measured total hippocampal formation volumes and subfield volumes with ultra-high field (7 Tesla), T1-weighted, structural magnetic resonance imaging, and FreeSurfer. Twenty-eight remitted patients and 22 healthy subjects were included as controls. We hypothesized to detect increased volumes after treatment in major depressive disorder.We did not detect treatment-related changes of total hippocampal or subfield volumes in patients with major depressive disorder. Secondary results indicated that the control group of untreated, stable remitted patients, compared with healthy controls, had larger volumes of the right hippocampal-amygdaloid transition area and right fissure at both measurement time points. Depressed patients exhibited larger volumes of the right subiculum compared with healthy controls at MRI-2. Exploratory data analyses indicated lower baseline volumes in the subgroup of remitting (n = 10) vs nonremitting (n = 10) acute patients.The results demonstrate that monoaminergic antidepressant treatment in major depressive disorder patients was not associated with volume changes in hippocampal subfields. Studies with larger sample sizes to detect smaller effects as well as other imaging modalities are needed to further assess the impact of antidepressant treatment on hippocampal subfields.

    View details for DOI 10.1093/ijnp/pyz030

    View details for PubMedID 31175352

    View details for PubMedCentralID PMC6672627

  • Modulations in resting state networks of subcortical structures linked to creativity. NeuroImage Schuler, A. L., Tik, M., Sladky, R., Luft, C. D., Hoffmann, A., Woletz, M., Zioga, I., Bhattacharya, J., Windischberger, C. 2019; 195: 311-319


    Creativity is a sine qua non ability for almost all aspects of everyday life. Although very profound behavioural models were provided by 21st century psychologists, the neural correlates of these personality features associated with creativity are largely unknown. Recent models suggest strong relationships between dopamine release and various creative skills. Herein, we employed functional connectivity analyses of resting-state functional magnetic imaging data in order to shed light on these neural underpinnings of creative aspects. For improved sensitivity, we performed the study at ultra-high magnetic field (7 T). Seed regions were defined based on subcortical (ventral tegmental area/substantia nigra, nucleus caudatus) activation foci of a remote associates task (RAT). In addition, bilateral PCC was used as seed region to examine the default-mode network. Network strength across subjects was regressed against a battery of psychological variables related to creativity. Dopaminergic network variations turned out to be indicative for individual differences in creative traits. In this regard, the caudate network showed stronger connectivity in individuals with higher extraversion measures, while connectivity with the midbrain network was found increased with higher ideational behaviour and emotional stability.

    View details for DOI 10.1016/j.neuroimage.2019.03.017

    View details for PubMedID 30935909

  • Antidepressant treatment, not depression, leads to reductions in behavioral and neural responses to pain empathy. Translational psychiatry Rütgen, M., Pletti, C., Tik, M., Kraus, C., Pfabigan, D. M., Sladky, R., Klöbl, M., Woletz, M., Vanicek, T., Windischberger, C., Lanzenberger, R., Lamm, C. 2019; 9 (1): 164


    Major depressive disorder (MDD) has been hypothesized to lead to impairments in empathy. Previous cross-sectional studies did not disentangle effects of MDD itself and antidepressant treatment. In this first longitudinal neuroimaging study on empathy in depression, 29 patients with MDD participated in two functional magnetic resonance imaging (fMRI) sessions before and after 3 months of antidepressant therapy. We compared their responses to an empathy for pain task to a group of healthy controls (N = 35). All participants provided self-report ratings targeting cognitive (perspective taking) and affective (unpleasant affect) aspects of empathy. To control for general effects on processing of negative affective states, participants additionally underwent an electrical pain task. Before treatment, we found no differences in empathic responses between controls and patients with MDD. After treatment, patients showed significant decreases in both affective empathy and activity of three a priori selected brain regions associated with empathy for pain. Decreases in affective empathy were moreover correlated with symptom improvement. Moreover, functional connectivity during the empathy task between areas associated with affective (anterior insula) and cognitive (precuneus) empathy decreased between sessions in the MDD group. Neither cognitive empathy nor responses to painful electrical shocks were changed after treatment. These findings contradict previous cross-sectional reports of empathy deficits in acute MDD. Rather, they suggest that antidepressant treatment reduces the aversive responses triggered by exposure to the suffering of others. Importantly, this cannot be explained by a general blunting of negative affect, as treatment did not change self-experienced pain.

    View details for DOI 10.1038/s41398-019-0496-4

    View details for PubMedID 31175273

    View details for PubMedCentralID PMC6555809

  • Correction to: The pulvinar nucleus and antidepressant treatment: dynamic modeling of antidepressant response and remission with ultra-high field functional MRI. Molecular psychiatry Kraus, C., Klöbl, M., Tik, M., Auer, B., Vanicek, T., Geissberger, N., Pfabigan, D. M., Hahn, A., Woletz, M., Paul, K., Komorowski, A., Kasper, S., Windischberger, C., Lamm, C., Lanzenberger, R. 2019; 24 (5): 772


    The author list was presented as last name, first name. The names should have been listed as:Christoph Kraus, Manfred Klöbl, Martin Tik, Bastian Auer, Thomas Vanicek, Nicole Geissberger, Daniela M. Pfabigan, Andreas Hahn, Michael Woletz, Katharina Paul, Arkadiusz Komorowski, Siegfried Kasper, Christian Windischberger, Claus Lamm, Rupert Lanzenberger.

    View details for DOI 10.1038/s41380-018-0032-6

    View details for PubMedID 29520037

    View details for PubMedCentralID PMC6755979

  • The pulvinar nucleus and antidepressant treatment: dynamic modeling of antidepressant response and remission with ultra-high field functional MRI. Molecular psychiatry Kraus, C., Klöbl, M., Tik, M., Auer, B., Vanicek, T., Geissberger, N., Pfabigan, D. M., Hahn, A., Woletz, M., Paul, K., Komorowski, A., Kasper, S., Windischberger, C., Lamm, C., Lanzenberger, R. 2019; 24 (5): 746-756


    Functional magnetic resonance imaging (fMRI) successfully disentangled neuronal pathophysiology of major depression (MD), but only a few fMRI studies have investigated correlates and predictors of remission. Moreover, most studies have used clinical outcome parameters from two time points, which do not optimally depict differential response times. Therefore, we aimed to detect neuronal correlates of response and remission in an antidepressant treatment study with 7 T fMRI, potentially harnessing advances in detection power and spatial specificity. Moreover, we modeled outcome parameters from multiple study visits during a 12-week antidepressant fMRI study in 26 acute (aMD) patients compared to 36 stable remitted (rMD) patients and 33 healthy control subjects (HC). During an electrical painful stimulation task, significantly higher baseline activity in aMD compared to HC and rMD in the medial thalamic nuclei of the pulvinar was detected (p = 0.004, FWE-corrected), which was reduced by treatment. Moreover, clinical response followed a sigmoid function with a plateau phase in the beginning, a rapid decline and a further plateau at treatment end. By modeling the dynamic speed of response with fMRI-data, perigenual anterior cingulate activity after treatment was significantly associated with antidepressant response (p < 0.001, FWE-corrected). Temporoparietal junction (TPJ) baseline activity significantly predicted non-remission after 2 antidepressant trials (p = 0.005, FWE-corrected). The results underline the importance of the medial thalamus, attention networks in MD and antidepressant treatment. Moreover, by using a sigmoid model, this study provides a novel method to analyze the dynamic nature of response and remission for future trials.

    View details for DOI 10.1038/s41380-017-0009-x

    View details for PubMedID 29422521

    View details for PubMedCentralID PMC6756007

  • Beware detrending: Optimal preprocessing pipeline for low-frequency fluctuation analysis. Human brain mapping Woletz, M., Hoffmann, A., Tik, M., Sladky, R., Lanzenberger, R., Robinson, S., Windischberger, C. 2019; 40 (5): 1571-1582


    Resting-state functional magnetic resonance imaging (rs-fMRI) offers the possibility to assess brain function independent of explicit tasks and individual performance. This absence of explicit stimuli in rs-fMRI makes analyses more susceptible to nonneural signal fluctuations than task-based fMRI. Data preprocessing is a critical procedure to minimise contamination by artefacts related to motion and physiology. We herein investigate the effects of different preprocessing strategies on the amplitude of low-frequency fluctuations (ALFFs) and its fractional counterpart, fractional ALFF (fALFF). Sixteen artefact reduction schemes based on nuisance regression are applied to data from 82 subjects acquired at 1.5 T, 30 subjects at 3 T, and 23 subjects at 7 T, respectively. In addition, we examine test-retest variance and effects of bias correction. In total, 569 data sets are included in this study. Our results show that full artefact reduction reduced test-retest variance by up to 50%. Polynomial detrending of rs-fMRI data has a positive effect on group-level t-values for ALFF but, importantly, a negative effect for fALFF. We show that the normalisation process intrinsic to fALFF calculation causes the observed reduction and introduce a novel measure for low-frequency fluctuations denoted as high-frequency ALFF (hfALFF). We demonstrate that hfALFF values are not affected by the negative detrending effects seen in fALFF data. Still, highest grey matter (GM) group-level t-values were obtained for fALFF data without detrending, even when compared to an exploratory detrending approach based on autocorrelation measures. From our results, we recommend the use of full nuisance regression including polynomial detrending in ALFF data, but to refrain from using polynomial detrending in fALFF data. Such optimised preprocessing increases GM group-level t-values by up to 60%.

    View details for DOI 10.1002/hbm.24468

    View details for PubMedID 30430691

    View details for PubMedCentralID PMC6587723

  • Ultra-high-field fMRI insights on insight: Neural correlates of the Aha!-moment. Human brain mapping Tik, M., Sladky, R., Luft, C. D., Willinger, D., Hoffmann, A., Banissy, M. J., Bhattacharya, J., Windischberger, C. 2018; 39 (8): 3241-3252


    Finding creative solutions to difficult problems is a fundamental aspect of human culture and a skill highly needed. However, the exact neural processes underlying creative problem solving remain unclear. Insightful problem solving tasks were shown to be a valid method for investigating one subcomponent of creativity: the Aha!-moment. Finding insightful solutions during a remote associates task (RAT) was found to elicit specific cortical activity changes. Considering the strong affective components of Aha!-moments, as manifested in the subjectively experienced feeling of relief following the sudden emergence of the solution of the problem without any conscious forewarning, we hypothesized the subcortical dopaminergic reward network to be critically engaged during Aha. To investigate those subcortical contributions to insight, we employed ultra-high-field 7 T fMRI during a German Version of the RAT. During this task, subjects were exposed to word triplets and instructed to find a solution word being associated with all the three given words. They were supposed to press a button as soon as they felt confident about their solution without further revision, allowing us to capture the exact event of Aha!-moment. Besides the finding on cortical involvement of the left anterior middle temporal gyrus (aMTG), here we showed for the first time robust subcortical activity changes related to insightful problem solving in the bilateral thalamus, hippocampus, and the dopaminergic midbrain comprising ventral tegmental area (VTA), nucleus accumbens (NAcc), and caudate nucleus. These results shed new light on the affective neural mechanisms underlying insightful problem solving.

    View details for DOI 10.1002/hbm.24073

    View details for PubMedID 29665228

    View details for PubMedCentralID PMC6055807

  • Unsmoothed functional MRI of the human amygdala and bed nucleus of the stria terminalis during processing of emotional faces. NeuroImage Sladky, R., Geissberger, N., Pfabigan, D. M., Kraus, C., Tik, M., Woletz, M., Paul, K., Vanicek, T., Auer, B., Kranz, G. S., Lamm, C., Lanzenberger, R., Windischberger, C. 2018; 168: 383-391


    Functional neuroimaging of the human amygdala has been of great interest to uncover the neural underpinnings of emotions, mood, motivation, social cognition, and decision making, as well as their dysfunction in psychiatric disorders. Yet, several factors limit in vivo imaging of amygdalar function, most importantly its location deep within the temporal lobe adjacent to air-filled cavities that cause magnetic field inhomogeneities entailing signal dropouts. Additionally, the amygdala and the extended amygdalar region consist of several substructures, which have been assigned different functions and have important implications for functional and effective connectivity studies. Here we show that high-resolution ultra-high field fMRI at 7T can be used to overcome these fundamental challenges for acquisition and can meet some of the demands posed by the complex neuroanatomy and -physiology in this region. Utilizing the inherently high SNR, we use an optimized preprocessing and data analysis strategy to demonstrate that imaging of the (extended) amygdala is highly reliable and robust. Using unsmoothed single-subject data allowed us to differentiate brain activation during processing of emotional faces in the central and basolateral amygdala and, for the first time, in the bed nucleus of the stria terminalis (BNST), which is critically involved in the neural mechanisms of anxiety and threat monitoring. We also provide a quantitative assessment of single subject sensitivity, which is relevant for connectivity studies that rely on time course extraction of functionally-defined volumes of interest.

    View details for DOI 10.1016/j.neuroimage.2016.12.024

    View details for PubMedID 28108394

  • Effects of testosterone treatment on hypothalamic neuroplasticity in female-to-male transgender individuals. Brain structure & function Kranz, G. S., Hahn, A., Kaufmann, U., Tik, M., Ganger, S., Seiger, R., Hummer, A., Windischberger, C., Kasper, S., Lanzenberger, R. 2018; 223 (1): 321-328


    Diffusion-weighted imaging (DWI) is used to measure gray matter tissue density and white matter fiber organization/directionality. Recent studies show that DWI also allows for assessing neuroplastic adaptations in the human hypothalamus. To this end, we investigated a potential influence of testosterone replacement therapy on hypothalamic microstructure in female-to-male (FtM) transgender individuals. 25 FtMs were measured at baseline, 4 weeks, and 4 months past treatment start and compared to 25 female and male controls. Our results show androgenization-related reductions in mean diffusivity in the lateral hypothalamus. Significant reductions were observed unilaterally after 1 month and bilaterally after 4 months of testosterone treatment. Moreover, treatment induced increases in free androgen index and bioavailable testosterone were significantly associated with the magnitude of reductions in mean diffusivity. These findings imply microstructural plasticity and potentially related changes in neural activity by testosterone in the adult human hypothalamus and suggest that testosterone replacement therapy in FtMs changes hypothalamic microstructure towards male proportions.

    View details for DOI 10.1007/s00429-017-1494-z

    View details for PubMedID 28819863

    View details for PubMedCentralID PMC5772168

  • Towards understanding rTMS mechanism of action: Stimulation of the DLPFC causes network-specific increase in functional connectivity. NeuroImage Tik, M., Hoffmann, A., Sladky, R., Tomova, L., Hummer, A., Navarro de Lara, L., Bukowski, H., Pripfl, J., Biswal, B., Lamm, C., Windischberger, C. 2017; 162: 289-296


    Transcranial magnetic stimulation (TMS) is a powerful non-invasive technique for the modulation of brain activity. While the precise mechanism of action is still unknown, TMS is applied in cognitive neuroscience to establish causal relationships between stimulation and subsequent changes in cerebral function and behavioral outcome. In addition, TMS is an FDA-approved therapeutic agent in psychiatric disorders, especially major depression. Successful repetitive TMS in such disorders is usually applied over the left dorso-lateral prefrontal cortex (DLPFC) and treatment response mechanism was therefore supposed to be based on modulations in functional networks, particularly the meso-cortico-limbic reward circuit. However, mechanistic evidence for the direct effects of rTMS over DLPFC is sparse. Here we show the specificity and temporal evolution of rTMS effects by comparing connectivity changes within 20 common independent components in a sham-controlled study. Using an unbiased whole-brain resting-state network (RSN) approach, we successfully demonstrate that stimulation of left DLPFC modulates anterior cingulate cortex (ACC) connectivity in one specific meso-cortico-limbic network, while all other networks are neither influenced by rTMS nor by sham treatment. The results of this study show that the neural correlates of TMS treatment response are also traceable in DLPFC stimulation of healthy brains and therefore represent direct effects of the stimulation procedure.

    View details for DOI 10.1016/j.neuroimage.2017.09.022

    View details for PubMedID 28912081

  • High-sensitivity TMS/fMRI of the Human Motor Cortex Using a Dedicated Multichannel MR Coil. NeuroImage Navarro de Lara, L. I., Tik, M., Woletz, M., Frass-Kriegl, R., Moser, E., Laistler, E., Windischberger, C. 2017; 150: 262-269


    To validate a novel setup for concurrent TMS/fMRI in the human motor cortex based on a dedicated, ultra-thin, multichannel receive MR coil positioned between scalp and TMS system providing greatly enhanced sensitivity compared to the standard birdcage coil setting.A combined TMS/fMRI design was applied over the primary motor cortex based on 1Hz stimulation with stimulation levels of 80%, 90%, 100%, and 110% of the individual active motor threshold, respectively. Due to the use of a multichannel receive coil we were able to use multiband-accelerated (MB=2) EPI sequences for the acquisition of functional images. Data were analysed with SPM12 and BOLD-weighted signal intensity time courses were extracted in each subject from two local maxima (individual functional finger tapping localiser, fixed MNI coordinate of the hand knob) next to the hand area of the primary motor cortex (M1) and from the global maximum.We report excellent image quality without noticeable signal dropouts or image distortions. Parameter estimates in the three peak voxels showed monotonically ascending activation levels over increasing stimulation intensities. Across all subjects, mean BOLD signal changes for 80%, 90%, 100%, 110% of the individual active motor threshold were 0.43%, 0.63%, 1.01%, 2.01% next to the individual functional finger tapping maximum, 0.73%, 0.91%, 1.34%, 2.21% next to the MNI-defined hand knob and 0.88%, 1.09%, 1.65%, 2.77% for the global maximum, respectively.Our results show that the new setup for concurrent TMS/fMRI experiments using a dedicated MR coil array allows for high-sensitivity fMRI particularly at the site of stimulation. Contrary to the standard birdcage approach, the results also demonstrate that the new coil can be successfully used for multiband-accelerated EPI acquisition. The gain in flexibility due to the new coil can be easily combined with neuronavigation within the MR scanner to allow for accurate targeting in TMS/fMRI experiments.

    View details for DOI 10.1016/j.neuroimage.2017.02.062

    View details for PubMedID 28254457

  • Effects of sex hormone treatment on white matter microstructure in individuals with gender dysphoria. NeuroImage Kranz, G. S., Seiger, R., Kaufmann, U., Hummer, A., Hahn, A., Ganger, S., Tik, M., Windischberger, C., Kasper, S., Lanzenberger, R. 2017; 150: 60-67


    Sex steroid hormones such as estradiol and testosterone are known to have organizing, as well as activating effects on neural tissue in animals and humans. This study investigated the effects of transgender hormone replacement therapy on white matter microstructure using diffusion tensor imaging. Female-to-male and male-to-female transgender participants were measured at baseline, four weeks and four months past treatment start and compared to female and male controls. We observed androgenization-related reductions in mean diffusivity and increases in fractional anisotropy. We also observed feminization-related increases in mean diffusivity and reductions in fractional anisotropy. In both transgender participants and controls, hormonal fluctuations were correlated with changes in white matter microstructure. Although the present study does not preclude regression to the mean as a potential contributing factor, the results indicate that sex hormones are - at least in part - responsible for white matter variability in the human brain. Studies investigating the effects of sex hormones on adult human brain structure may be an important route for greater understanding of the psychological differences between females and males.

    View details for DOI 10.1016/j.neuroimage.2017.02.027

    View details for PubMedID 28196668

  • Neurobiological differences in mental rotation and instrument interpretation in airline pilots. Scientific reports Sladky, R., Stepniczka, I., Boland, E., Tik, M., Lamm, C., Hoffmann, A., Buch, J. P., Niedermeier, D., Field, J., Windischberger, C. 2016; 6: 28104


    Airline pilots and similar professions require reliable spatial cognition abilities, such as mental imagery of static and moving three-dimensional objects in space. A well-known task to investigate these skills is the Shepard and Metzler mental rotation task (SMT), which is also frequently used during pre-assessment of pilot candidates. Despite the intuitive relationship between real-life spatial cognition and SMT, several studies have challenged its predictive value. Here we report on a novel instrument interpretation task (IIT) based on a realistic attitude indicator used in modern aircrafts that was designed to bridge the gap between the abstract SMT and a cockpit environment. We investigated 18 professional airline pilots using fMRI. No significant correlation was found between SMT and IIT task accuracies. Contrasting both tasks revealed higher activation in the fusiform gyrus, angular gyrus, and medial precuneus for IIT, whereas SMT elicited significantly stronger activation in pre- and supplementary motor areas, as well as lateral precuneus and superior parietal lobe. Our results show that SMT skills per se are not sufficient to predict task accuracy during (close to) real-life instrument interpretation. While there is a substantial overlap of activation across the task conditions, we found that there are important differences between instrument interpretation and non-aviation based mental rotation.

    View details for DOI 10.1038/srep28104

    View details for PubMedID 27323913

    View details for PubMedCentralID PMC4914984